Reevaluation of the Effects of Castration on Naloxone-Sensitive Opiate Receptors in the Male Rat Brain

Abstract

There is a great deal of conflicting data regarding the issue of whether androgens influence opiate receptors in the whole male rat brain. Although Hahn and Fishman initially reported that long-term castration produced a large increase in the density of opiate-binding sites, relative to controls, no other independent group has been able to replicate these results. Recently, the former investigators reported that procedural differences could fully account for the discrepancies in the literature. Because of the importance of demonstrating a direct biochemical association between steroid- and endogenous opioid-containing neuronal elements in brain, we have reexamined the issue of whether long-term castration influences opiate receptors in whole male rat brain. To accomplish this goal, we incorporated all of the critical procedural variables which were identified by Hahn and Fishman as possible confounding variables in such studies. Our results clearly demonstrate that under identical conditions, we were unable to replicate the results of these investigators. In addition, we attempted to use other paradigms in an attempt to resolve this long-standing controversy in the literature, but these attempts were also unsuccessful. We are unable to explain our inability to replicate the results of Hahn and Fishman. However, it should be noted that at least 4 independent groups have now failed to reproduce their findings. Thus, it appears that the intrinsically attractive hypothesis that steroids influence opiate receptors cannot be addressed using whole brain analysis or relatively crude areas of brain and relatively nonspecific opiate ligands. Rather, it seems probable that this issue can only be addressed using techniques which recognize the marked regional localization of steroid effects and multiple opioid receptor subtypes in brain (e.g. autoradiography).

Revaluation of the Role of Alpha₂-Adrenoreceptors in Morphine-Stimulated Release of Growth Hormone

“…Testosterone is known to re verse the effects of castration on clonidine-induced GH release [15,16] and estradiol increased alpha2-receptor density in some brain areas [24]; castration may alter the opioid receptors [25] although this conclusion has not been confirmed [26]. In the present study it has been found that the effect of morphine on the GH secretion remained unchanged in castrates while the secretion of this hormone after clonidine treatment was signifi cantly blunted.…”

Steroidal and Photoperiodic Regulation of Opiate Binding in Male Golden Hamsters

“…Our finding that castration elevates specific opiate binding in several brain areas, including the medial amygdala, MPN, and BNST, is relevant to the report of Hahn and Fishman (16) that orchidectomy elevates 3H-naloxone binding in whole rat brain. This finding (16) has proven difficult to replicate (17,18), perhaps because these experiments involved homogenization and preparation of membrane extracts of large areas of brain and did not afford the spatial resolution provided by in vitro autoradiography. Since physiologically relevant environmental signals (in this case, photoperiod) may regulate the influence of androgens upon opiate receptors, differences in conditions under which animals are housed may contribute to discrepancies between laboratories.…”

Effects of acute and chronic administrations of naloxone on plasma luteinizing hormone and prolactin in broody turkey hens (Meleagris gallopavo)

“…There is no ready explanation for these discrepancies in effects However, the mode of administration and/or the doses of naloxone used may be the cause ofthese divergent effects. On the other hand, naloxone has a wide range of affinity for different types ofopioid receptors (Cicero et al 1987); therefore its divergent effects on LH secretion may also be explained by different receptors being accessed after the acute injection experiment than during the chronic infusion experiment. Sakurai et al (1986) support the notion that opioids may also be Feed intake and water consumption can be involved in the control of basal secretion of stimulated by naloxone treatment of chicks LH in broody turkey hens.…”